Analysis of overall survival (OS) and relapse-free-survival (RFS) in the phase 1b clinical trial of anti–PD-1 ab (toripalimab) plus intralesional injection of OrienX010 in stage Ⅳ melanoma with liver metastases.
Authors: Chuanliang Cui, Bin Lian, Xuan Wang, Shanshan Yin, Yue Cong, Yue Yang, Zhihong Chi, Lu Si, Xinan Sheng, Yan Kong, Bixia Tang, Lili Mao, Xue Bai, Xieqiao Yan, Siming Li, Li Zhou, Jie Dai, Jun Guo
Journal: Journal of Clinical Oncology (2022)

9551 Background: Advanced melanoma with liver metastasis has reduced response to anti-PD-1 monotherapy with ORR of 4.3% in a pooled analysis, and initial results of the phase 1b trial, systemic toripalimab combined with intrahepatic OrienX010 injection - a HSV-1-derived oncolytic virotherapy with expression of GM-CSF had shown its efficacy. Here we report the RFS and OS outcomes. Methods: Eligible pts included those over 18 with injectable liver metastasis confirmed by biopsy with or without extra-hepatic metastasis; the ocular melanoma and brain metastasis were excluded. Pts received intravenous toripalimab Q2W combined with ultrasound guided intratumoral injection of OrienX010 Q2W (8×10 7 pfu/ml, 10ml per injection) until intolerance or disease progression per iRECIST criteria. Liver biopsy would be performed at baseline and first tumor evaluation (8-12weeks). The primary endpoint was toxicity; secondary endpoints included ORR, DCR and PFS. Results: From Jul 2019 to Jan 2022, 23 pts were eligible and enrolled. Baseline characteristics: median age 69 yrs; primary: mucosal 60.9%, cutaneous 13.0%, unknown primary 13.0%, acral 13.0%; gene mutation status: Braf 17.4%, Nras 4.3%; 69.6% got extra-hepatic metastasis: regional or distant lymph node 56.3%, lung 37.5%, bone 31.3%; LDH＞ULN 26.1%; median size of injected lesions: 35mm(10-94mm); median number of liver metastasis: 7(1-10); median number of injection: 10 (3-36). Among these pts, 20 pts could be evaluated for efficacy. The median PFS was 7.0 months (95%CI: 4.3-9.7 months) and the median OS was 18.6 months (95%CI: 13.4-23.7 months) with a median follow-up time of 19.8 months (range, 0.9-29.7). The global ORR by investigator was 15% (3/20), DCR 50% (10/20); the response rate was 35%(7/20) for injected lesions, 27.8%(5/18) for non-injected lesions in liver, and 26.7% (4/15) for extra-hepatic metastases. Biopsies of 15 pts for injected lesions at 8 to 12 weeks after first injection were examined to determine the situation of TIL infiltration. Among them, the median PFS of the pts (7/15) with impressive TIL infiltration (Brisk n = 4 and Nonbrisk n = 3 according to the definition of AJCC 8th edition) was 7.8 months (95%CI: 2.8-12.8 months) versus 4.1 months (95%CI: 0-9.1 months) of the pts without impressive TIL infiltration. For pts（21.7%( 2 PR and 3 SD)）with no melanoma cells residual by immunohistochemistry in biopsies the median PFS was 13.8 months (95%CI: 4.0-23.6 months), and it was much longer than that of other pts which was 5.6 months (95%CI: 2.4-8.8 months). The median OS of the pts with no melanoma cells was 19.7 months (95%CI: 7.5-31.9 months). Conclusions: Systemic toripalimab combined with intrahepatic OrienX010 injection has shown remarkable long PFS and OS in melanoma pts with liver metastases. Clinical trial information: NCT04206358.